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Cortical field boundaries of sensory areas can be physiologically defined. The delineation of the human auditory cortical architecture remains incomplete. Here we used systematic variation of pitch and duration of sinusoidal tones to define auditory cortical fields along Heschl's gyrus with a silent, event-related fMRI scanning technique that allowed us to determine spatially small shifts of neuronal responses. Thus, we were able to establish higher-resolution tonotopic maps. Acoustic intervals of two octaves correspond to an average 2-mm anatomical distance along Heschl's gyrus. We also demonstrate that one tonotopic map with a medio-lateral low- to high-frequency gradient is located on the lateral half of Heschl's gyrus, which might correspond to field R in primates. Furthermore, we studied cortical responses to brief (50-ms) transients with fMRI and demonstrate that silent, event-related fMRI is capable of measuring significant blood oxygen level-dependent effect to such brief events in the acoustic domain. Our results add to current knowledge on the number and precise localization of multiple tonotopic maps in human auditory cortex. More specifically, they support the hypothesis that there may be two primary auditory cortical fields with mirror tonotopic organization on Heschl's gyrus in man.

The feasibility of mapping transient, randomly occurring neuropsychological events using independent component analysis (ICA) was evaluated in an auditory sentence-monitoring fMRI experiment, in which prerecorded short sentences of random content were presented in varying temporal patterns. The efficacy of ICA on fMRI data with such temporal characteristics was assessed by a series of simulation studies, as well as by human activation studies. The effects of contrast-to-noise ratio level, spatially varied hemodynamic response within a brain region, time lags of the responses among brain regions, and different simulated activation locations on the ICA were investigated in the simulations. Component maps obtained from the auditory sentence-monitoring experiments in each subject using ICA showed distinct activation in bilateral auditory and language cortices, as well as in superior sensorimotor cortices, consistent with previous PET studies. The associated time courses in the activated brain regions matched well to the timing of the sentence presentation, as evidenced by the recorded button-press response signals. Methods for ICA component ordering that may rank highly the components of primary interest in such experiments were developed. The simulation results characterized the performance of ICA under various conditions and may provide useful information for experimental design and data interpretation.

Neural substrates of behavioral inhibitory control have been probed in a variety of animal model, physiologic, behavioral, and imaging studies, many emphasizing the role of prefrontal circuits. Likewise, the neurocircuitry of emotion has been investigated from a variety of perspectives. Recently, neural mechanisms mediating the interaction of emotion and behavioral regulation have become the focus of intense study. To further define neurocircuitry specifically underlying the interaction between emotional processing and response inhibition, we developed an emotional linguistic go/no-go fMRI paradigm with a factorial block design which joins explicit inhibitory task demand (i.e., go or no-go) with task-unrelated incidental emotional stimulus valence manipulation, to probe the modulation of the former by the latter. In this study of normal subjects focusing on negative emotional processing, we hypothesized activity changes in specific frontal neocortical and limbic regions reflecting modulation of response inhibition by negative stimulus processing. We observed common fronto-limbic activations (including orbitofrontal cortical and amygdalar components) associated with the interaction of emotional stimulus processing and response suppression. Further, we found a distributed cortico-limbic network to be a candidate neural substrate for the interaction of negative valence-specific processing and inhibitory task demand. These findings have implications for elucidating neural mechanisms of emotional modulation of behavioral control, with relevance to a variety of neuropsychiatric disease states marked by behavioral dysregulation within the context of negative emotional processing.

Functional MRI during performance of a validated mental rotation task was used to assess a neurobiological basis for sex differences in visuospatial processing. Between-sex group analysis demonstrated greater activity in women than in men in dorsalmedial prefrontal and other high-order heteromodal association cortices, suggesting women performed mental rotation in an effortful, "top-down" fashion. In contrast, men activated primary sensory cortices as well as regions involved in implicit learning (basal ganglia) and mental imagery (precuneus), consistent with a more automatic, "bottom-up" strategy. Functional connectivity analysis in association with a measure of behavioral performance showed that, in men (but not women), accurate performance was associated with deactivation of parieto-insular vestibular cortex (PIVC) as part of a visual-vestibular network. Automatic evocation by men to a greater extent than women of this network during mental rotation may represent an effective, unconscious, bottom-up neural strategy which could reasonably account for men's traditional visuospatial performance advantage.

A new single-shot echo-planar imaging (EPI) sequence with interleaved z-shim and optimized compensation for susceptibility-induced signal loss is proposed in this paper. Experiments on human brain demonstrated that the new method is able to regain signal dropout in brain areas with severe susceptibility-induced local gradients, while its image acquisition speed is comparable to that of conventional single-shot EPI techniques. Significant signal-to-noise ratio improvements were demonstrated in the ventral prefrontal and lateral temporal lobes with the new technique compared to a conventional EPI. Brain activation experiments with a bilateral finger-tapping task were performed with intentionally introduced local gradients near the left sensorimotor cortex, by a small gadolinium (Gd)-doped bottle placed on the left side of the head. The results of the functional experiments showed that the interleaved z-shim EPI sequence effectively recovered the signal loss caused by the Gd-doped bottle and reliably detected activation signals in bilateral sensorimotor regions, while the activation signals on the left side diminished considerably in a conventional EPI technique. The new technique, with the capability of reducing susceptibility artifacts and rapid scanning speed, may be particularly useful for event-related functional MRI experiments in the base of the brain, which are of great importance in neuropsychiatric studies.

A perfusion-based event-related functional MRI method for the study of brain activation is presented. In this method, cerebral blood flow (CBF) was measured using a recently developed multislice arterial spin-labeling (ASL) perfusion imaging method with rapid spiral scanning. Temporal resolution of the perfusion measurement was substantially improved by employing intertrial subtraction and stimulus-shifting schemes. Perfusion and blood oxygenation level-dependent (BOLD) signals were obtained simultaneously by subtracting or adding the control and labeled images, respectively, in the same data sets. The impulse response function (IRF) of perfusion during brain activation was characterized for multiple stimulus durations and compared to the simultaneously acquired BOLD response. The CBF response curve preceded the BOLD curve by 0.21 s in the rising phase and 0.64 s in the falling phase. Linear additivity of the CBF and BOLD responses was assessed with rapidly repeated stimulations within single trials, and departure from linearity was found in both responses, characterized as attenuated amplitude and delayed rising time. Event-related visual and sensorimotor activation experiments were successfully performed with the new perfusion technique.

METHODS MRI experiments were done on a 1.5T GE-LX2 scanner on normal subjects. Cerebral perfusion was measured with a modified multislice perfusion imaging technique in which pulsed arterial spin-labeling was combined with a fast spiral scan (10). Temporal resolution was improved by using inter-trial subtraction and stimulus shifting (9). In the perfusion sequence, gradient-echo signals were acquired with TI =1.2s, TE=22ms, and TR =2s. The echo time was chosen to allow for detection of perfusion and BOLD signals simultaneously. Perfusion and BOLD signals were obtained by subtracting or adding the control and labeled perfusion images respectively in the same data sets. Brain activation experiments were performed with black-white flashing checkerboard (8Hz) presented with a back projector. Multiple stimuli were presented within single trials to address the linearity of the impulse response of the brain perfusion. Four types of stimuli were used in the experiments, as shown in Fig.1. In experiment I, a visual stimulus of Is duration was delivered at the start of each trial. In experiment II, two stimuli (1s duration) with a interval of 2s were delivered. In experiment III, three stimuli (1s duration) with intervals of 2s were delivered. In experiment IV, two stimuli (1s duration) with a interval of 5s were delivered. Inter-stimulus interval (ISI) was 18s, and 48 trials were acquired, in all experiments.